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The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation.

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Saldin, LT; Klimak, M; Hill, RC; Cramer, MC; Huleihel, L; Li, X; Quidgley-Martin, M; Cardenas, D; Keane, TJ; Londono, R; Hussey, G; Kelly, L ...
Published in: Journal of immunology and regenerative medicine
August 2021

Macrophages are capable of extreme plasticity and their activation state has been strongly associated with solid tumor growth progression and regression. Although the macrophage response to extracellular matrix (ECM) isolated from normal tissue is reasonably well understood, there is a relative dearth of information regarding their response to ECM isolated from chronically inflamed tissues, pre-neoplastic tissues, and neoplastic tissues. Esophageal adenocarcinoma (EAC) is a type of neoplasia driven by chronic inflammation in the distal esophagus, and the length of the esophagus provides the opportunity to investigate macrophage behavior in the presence of ECM isolated from a range of disease states within the same organ.Normal, metaplastic, and neoplastic ECM hydrogels were prepared from decellularized EAC tissue. The hydrogels were evaluated for their nanofibrous structure (SEM), biochemical profile (targeted and global proteomics), and direct effect upon macrophage (THP-1 cell) activation state (qPCR, ELISA, immunolabeling) and indirect effect upon epithelial cell (Het-1A) migration (Boyden chamber).Nanofibrous ECM hydrogels from the three tissue types could be formed, and normal and neoplastic ECM showed distinctive protein profiles by targeted and global mass spectroscopy. ECM proteins functionally related to cancer and tumorigenesis were identified in the neoplastic esophageal ECM including collagen alpha-1(VIII) chain (COL8A1), lumican, and elastin. Metaplastic and neoplastic esophageal ECM induce distinctive effects upon THP-1 macrophage signaling compared to normal esophageal ECM. These effects include activation of pro-inflammatory IFNγ and TNFα gene expression and anti-inflammatory IL1RN gene expression. Most notably, neoplastic ECM robustly increased macrophage TNFα protein expression. The secretome of macrophages pre-treated with metaplastic and neoplastic ECM increases the migration of normal esophageal epithelial cells, similar behavior to that shown by tumor cells. Metaplastic ECM shows similar but less pronounced effects than neoplastic ECM suggesting the abnormal signals also exist within the pre-cancerous state.A progressively diseased ECM, as exists within the esophagus exposed to chronic gastric reflux, can provide insights into novel biomarkers of early disease and identify potential therapeutic targets.

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Published In

Journal of immunology and regenerative medicine

DOI

EISSN

2468-4988

ISSN

2468-4988

Publication Date

August 2021

Volume

13

Start / End Page

100037
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Saldin, L. T., Klimak, M., Hill, R. C., Cramer, M. C., Huleihel, L., Li, X., … Badylak, S. F. (2021). The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation. In Journal of immunology and regenerative medicine (Vol. 13, p. 100037). https://doi.org/10.1016/j.regen.2020.100037
Saldin, Lindsey T., Molly Klimak, Ryan C. Hill, Madeline C. Cramer, Luai Huleihel, Xue Li, Maria Quidgley-Martin, et al. “The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation.” In Journal of Immunology and Regenerative Medicine, 13:100037, 2021. https://doi.org/10.1016/j.regen.2020.100037.
Saldin LT, Klimak M, Hill RC, Cramer MC, Huleihel L, Li X, et al. The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation. In: Journal of immunology and regenerative medicine. 2021. p. 100037.
Saldin, Lindsey T., et al. “The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation.Journal of Immunology and Regenerative Medicine, vol. 13, 2021, p. 100037. Epmc, doi:10.1016/j.regen.2020.100037.
Saldin LT, Klimak M, Hill RC, Cramer MC, Huleihel L, Li X, Quidgley-Martin M, Cardenas D, Keane TJ, Londono R, Hussey G, Kelly L, Kosovec JE, Lloyd EJ, Omstead AN, Zhang L, Nieponice A, Jobe B, Hansen K, Zaidi AH, Badylak SF. The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation. Journal of immunology and regenerative medicine. 2021. p. 100037.
Journal cover image

Published In

Journal of immunology and regenerative medicine

DOI

EISSN

2468-4988

ISSN

2468-4988

Publication Date

August 2021

Volume

13

Start / End Page

100037